Synthesis, and Helix or Hairpin-Turn Secondary Structures of ‘Mixed’α/β-Peptides Consisting of Residues with Proteinogenic Side Chains and of 2-Amino-2-methylpropanoic Acid (Aib)

Abstract

Twelve peptides, 1–12, have been synthesized, which consist of alternating sequences of α- and β-amino acid residues carrying either proteinogenic side chains or geminal dimethyl groups (Aib). Two peptides, 13 and 14, containing 2-methyl-3-aminobutanoic acid residues or a ‘random mix’ of α-, β2-, and β3-amino acid moieties were also prepared. The new compounds were fully characterized by CD (Figs. 1 and 2), and 1H- and 13C-NMR spectroscopy, and high-resolution mass spectrometry (HR-MS). In two cases, 3 and 14, we discovered novel types of turn structures with nine- and ten-membered H-bonded rings forming the actual turns. In two other cases, 8 and 11, we found 14/15-helices, which had been previously disclosed in mixed α/β-peptides containing unusual β-amino acids with non-proteinogenic side chains. The helices are formed by peptides containing the amino acid moiety Aib in every other position, and their backbones are primarily not held together by H-bonds, but by the intrinsic conformations of the containing amino acid building blocks. The structures offer new possibilities of mimicking peptide–protein and protein–protein interactions (PPI).